Chromaffin cells of the adrenal medulla continue to serve as a powerful tool to explore the field of neurohumoral secretion. In 1981 PI introduced a preparation to study catecholamine (CA) secretion from the isolated perfused adrenal gland of the rat. Using this preparation a number of physiological and pharmacological properties of secretion have been established. Most recently, several new observations have been made which made, which are of potential importance. The observations are as follows: 1) Secretion of CA is induced by nicotine as well as muscarine. Nicotine enhances influx of Ca45, whereas muscarine does not, although muscarine-evoked secretion is dependent on calcium. Nicotine-evoked secretion is desensitized within 20 min but muscarine-evoked is not up to 45 min. - a possibility of differential routes of mobilization of calcium and its utilization in exocytosis. 2) As long as 2 hr of continuous perfusion with 55 mM K-Krebs solution causes a pronounced secretion of CA, with only a modest degree of desensitization. Excess K-evoked secretion is totally dependent on calcium - a possibility of slow inactivation of calcium channels. 3) A marked secretion of CA obtained during perfusion with 55 mM K-Krebs solution is not associated with a reduction in the medullary CA content; however, after blockade of tyrosine hydroxylase there was a significant reduction in CA content - a possibility of reutilization of chromaffin storage vesicles. 4) Secretion of CA evoked by stimulation of splanchnic nerves at higher frequencies is more effectively reduced by cholinergic receptor antagonists than that evoked at lower frequencies - a possibility of another transmitter, in addition to acetylcholine, (ACh), released from splanchnic nerves to evoke secretion of CA. 5) Protein kinase C activator (phorbol esters) potentiate CA secretion and Ca45 uptake initiated by nicotine. Phorbol esters have no effect on muscarine-evoked secretion. cAMP activator (forskolin) potentiates CA secretion evoked by nicotine as well as muscarine - a possibility of intracellular messengers participating at different steps of exocytosis to evoke secretion. Biochemical, physiological and pharmacological experiments have been designed to discern each of the above possibilities in hope of extending our understanding of the secretory mechanism.